Despite the advances in the neurophysiological study of sleep, the primary mechanisms and projection pathways exerting control over state-dependent neuronal activity in brain are largely unknown. Alterations in the activity of cell populations in the thalamus play an important role in much of the phenomenology of sleep and waking. In as much as the thalamus is not a primary generating mechanism for the states of arousal, it is hypothesized that extrathalamic mechanisms may account for the observed coupling of thalamic activity with state. Interactions among extrathalamic and intrathalamic mechanisms and the intrinsic properties of thalamic neurons contribute to the manifestations of sleep and wake phenomena in the thalamus. The proposed experiments are designed to add to knowledge about thalamic mechanisms through use of animal preparations that exhibit sleep and waking. These experiments will identify the neurotransmitter-receptor interactions subserving state regulation of thalamic neuronal activity in waking, rapid eye movement (REM) sleep, and slow wave sleep. This proposal deals specifically with the role of gamma-aminobutyric acid (GABA) inhibitory mechanisms and also the facilitatory influences of the biogenic amines, norepinephrine and histamine. Pharmacological agents directed at specific receptors will be microiontophoretically applied to electrophysiologically identified neurons, monitored extracellularly. Responses will be recorded in three thalamic nuclei, the lateral geniculate (LGN), the ventrobasal complex (VB), and the thalamic reticular nucleus (TRN), in unanesthetized rats, spontaneously cycling through waking and sleep states. Effects of agents that specifically antagonize and potentiate synaptic transmission will permit identification of the neurotransmitter-receptor interactions mediating the control of state-dependent activity.